ArticleAutophagy2016
Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- Reimagining the contribution of iron in Parkinson's disease.Neurobiology of disease · 2026Review
- HIV Tat-activated microglial extracellular vesicles induce neuronal iron dysregulation and synaptodendritic injury.Cell communication and signaling : CCS · 2026Article
- Regulation of Ferroptosis Sensitivity in Hepatocellular Carcinoma Cells by Lysosomal Ion Channels TPC2 and TRPML1.Antioxidants (Basel, Switzerland) · 2026Article
- Involvement of endolysosome iron in HIV-1 gp120-, morphine-, and iron supplementation-induced disruption of the reactive species interactome and induction of neurotoxicity.Redox report : communications in free radical research · 2025Article
- The interplay of iron, oxidative stress, and α-synuclein in Parkinson's disease progression.Molecular medicine (Cambridge, Mass.) · 2025Review
- Article
- Iron improves the antiviral activity of NK cells.Frontiers in immunology · 2024Article
- Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review).International journal of molecular medicine · 2023Review
- Imbalance of Essential Metals in Traumatic Brain Injury and Its Possible Link with Disorders of Consciousness.International journal of molecular sciences · 2023Review
- Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death.NeuroImmune pharmacology and therapeutics · 2023Article
- Structure and Function of Plant and Mammalian TPC Channels.Handbook of experimental pharmacology · 2023Article
- Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.Cell death & disease · 2022Article
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- HIV-1 gp120-Induced Endolysosome de-Acidification Leads to Efflux of Endolysosome Iron, and Increases in Mitochondrial Iron and Reactive Oxygen Species.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Review
- Endolysosome iron restricts Tat-mediated HIV-1 LTR transactivation by increasing HIV-1 Tat oligomerization and β-catenin expression.Journal of neurovirology · 2021Article
- A modified density gradient proteomic-based method to analyze endolysosomal proteins in cardiac tissue.iScience · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endolysosomal iron storage, cytosolic iron levels are modulated by NAADP, and increased cytosolic iron is detected when overexpressing active, but not inactive TPCNs, indicating that these channels can modulate endolysosomal iron release. Cell death triggered by altered intralysosomal iron handling is abrogated in the presence of an NAADP antagonist or when inhibiting RAB7A activity. Taken together, our results suggest that increased endolysosomal iron causes cell death associated with increased cytosolic oxidative stress as well as autophagic impairments, and these effects are subject to modulation by endolysosomal ion channel activity in a RAB7A-dependent manner. These data highlight alternative therapeutic strategies for neurodegenerative disorders associated with increased intracellular iron load.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.